Device for photodynamic diagnosis or treatment

ABSTRACT

An endoscopic or microscopic apparatus for diagnosis by means of a light-induced reaction in biologic tissue &#34;in vivo&#34; which is created by a photo-amboceptor or by autofluorescence is provided. The inventive apparatus is characterized by the feature that at least one reference wavelength lambdar is provided which is longer by up to 2Deltalambda at maximum or smaller than the wavelength lambdas at the point of intersection.

FIELD OF THE INVENTION

The present invention relates to an apparatus for the “in vivo”diagnosis by means of a light-induced reaction created by an endogenousor exogenous photo-amboceptor.

In order to trigger a light-induced reaction in biologic systems aphoto-amboceptor is administered to the patient in a concentration of afew mg/kg body weight.

PRIOR ART

Typical photo-amboceptors or sensitisers are Photofrin or Photosan,which present a basic hemato-porphyrin framework structure,protoporphyrin IX induced by δ-amino-laevulic acid (ALA) (PPIX), whichhas been used in urology and dermatology for a short time,9-Oac-tetramethoxy porphycene, benzoporphyrin derivatives, as-partylchlorine E₆, m-tetrahydroxyphenyl chlorine, Sn(IV) etiopurpurine orZn(II) phthalocyanine.

These substances accumulate in tumour tissues in a concentrationincreased by roughly two to fifteen times. This selective concentrationin tumour tissue is the decisive basis of the photodynamic diaghosis(PDD) and photodynamic therapy (PDT).

For diagnosis the tissue to be analysed is irradiated after anappropriate waiting period following the administration of thephoto-amboceptor, with blue or violet light—in known devices with laserlight almost exclusively. The photo-amboceptor, which is present in anincreased concentration in tumour tissue, is excited by this light anddisplays in response a typical red fluorescence by which the tumour canbe localized.

Apart from fluorescence—which is produced by a photo-amboceptoraccumulated in the tissue—the so-called autofluorescence of the tissuemay be triggered, too, which is brought about by endogenous fluorescentpigments. In this case mostly blue or ultraviolet light is used forexcitation as well.

In dependence on the respective photo-amboceptors used, the photodynamicdiagnosis (PDD) entails certain problems. When photofrin and photosan-3are used as photo-amboceptors in photodynamic diagnosis highly complexengineering devices are required for the detection of fluorescencebecause, on account of interfering autofluorescence fractions, only verycomplex computer-assisted image processing techniques and highlysensitive cameras with residual-light intensifier are suitable for anappropriate detection of the fluorescence in tumor tissue.

When δ-aminolaevulic acid (ALA) is used the induced fluorescence isstrong enough for recognition merely by visual inspection.

However, the fluorescence achieved by means of δ-aminolaevulic acid doesnot furnish an optimum quality of the image which is to be recorded aspart of the diagnosis. This is due, inter alia, to variabilities of theoptical tissue parameters which take an influence on the fluorescentintensity in a non-specific manner.

It is moreover known to use photo-amboceptors for photodynamic therapy(PDT). In this respect reference is made to the document WO 93/20810,which is, by the way, also referred to explicitly with respect to theexplanation of all terms and steps of operation which are not describedhere in more details.

The devices used for photodynamic diagnosis—which is also referred to asfluorescent diagnosis—or for photodynamic therapy, respectively, whichare also termed “PDD” or “PDT” devices, comprise an illuminating system,a light-feeding unit which directs the light from the illuminating unitto the tissue region to be diagnosed and/or treated, and an imaging, animage-recording and possibly an image-transmitting unit which images thelight coming from the tissue region into a proximal image plane.

The illuminating system and the light-supplying unit define the path ofthe illuminating beam whilst the imaging, the image-recording andpossibly the image-transmitting unit define the path of the observationbeam.

In an endoscopic PDD device the light-supplying unit consists of thelight guide, which connects the illuminating system to the light guideconnector of the endoscope, for instance, and the illuminating lightguide of the endoscope. The light guide may be a quartz light guide or afluid light guide, for instance. Fluid or quartz light guides offer abetter transmission in the blue or violet range than standard glasslight guides. The endoscope lens, which is disposed on the distal endand covers the tissue range illuminated by the light emerging from theilluminating light guide, constitutes the image-recording unit; theimage of the lens is picked up, for instance, by means of one or severalCCD receivers which serve as opto-electronic image converter unit. Whenthe CCD receiver is disposed on the proximal end the lens image istransmitted by a relay lens system or an imaging fiber bundle whichhence fulfill the function of the image-transmitting unit.

In the PCT application PCT/DE 96/01831, which is not a priorpublication, it has been proposed to perform endoscopic photodynamicdiagnosis and therapy by means of an apparatus in which a “source ofwhite light” is used as light source rather than a laser, i.e. a lightsource which generates incoherent light in the wavelength range of atleast from 390 to 650 nm. The light from the light source is fed via afocusing unit into the fiber optic light guide.

The aforementioned application contains moreover the proposal toharmonize the spectral internal transmittance factor or the (spectral)transmission function, respectively, of the light-feeding unit with thespectral internal transmittance factor or the (spectral function),respectively, of the imaging or image-recording unit in such a way thatonly a fraction of the light reflected on the irradiated tissuecontributes to the production of the image, which is so dimensioned thatthe fluorescent image will not be glared or blanketed by this“background picture”.

Filter systems are used, as a rule, to set the transmission function.The filter systems so far proposed entail the disadvantage, however,that small errors due to tolerances are sufficient to result in majorvariations of the reflected light quantity which contributes to theproduction of the image, which errors occur particularly in terms of theedge position and the steepness of the transmission edge. This effect,in its turn, results in a major change of the ratio between thefluorescent light and the background light.

When, for instance, the filter graph of the filter system introducedinto the path of the illuminating beam is shifted towards shorterwavelengths as a result of manufacturing or assembly faults—tilting ofthe filter, etc.—the overlapping of the transmission zones of the filtersystems introduced into the paths of the illuminating and observationbeams is practically reduced to “zero” in the event of small shiftsalready so that a background image is not obtained as a result of thedirectly reflected light and only a fluorescent image is achieved.

Vice versa, with a small shift towards longer wavelengths already anexcessive overlapping is achieved so that the fluorescent image isblanketed by the visible (“non”-fluorescent) background picture.

Moreover, a variation of the steepness of the transmission edge alsodisplaces the position of the transmission graph in the lowertransmission range so that this error requires compensation like an edgeposition error. In the upper range the overall transmission is, as amatter of fact, subjected only to a slight change.

Similar problems occur also in devices where a photodynamic diagnosis isperformed by means of a microscope and particularly a surgicalmicroscope. Appropriate devices are described in the European Patent EP0 241 268 A1 or the U.S. Pat. No. 5,371,624.

The problems which may occur in filter selection are described also inthe U.S. Pat. No. 4,056,724—cf. FIG. 14 in particular.

In all other respects explicit reference is made to these prior artdocuments as far as the explanation of all terms is concerned which arenot described here in details.

BRIEF DESCRIPTION OF THE INVENTION

The present invention is based on the problem of proposing a spectralinternal transmittance characteristic or a transmission function for thepath of the illuminating beam and/or the path of the observation beam,in which tolerance-induced errors, particularly in terms of the edgeposition and the steepness of the transmission edges, produce distinctlylower effects than other systems as far as the ratio between the lightquantities of the fluorescent light and the directly reflected light isconcerned which contributes to the production of the image.

Inventive solutions to this problem are defined in Patent Claim 1.Improvements of the invention are the subject matters of Claims 2 to 9.The Claims 10 and 11 relate to filters for use in a PDD apparatus.

The invention is based on the fundamental idea of designing thetransmission graphs in such a way that at least one of the transmissiongraphs presents a section having a “flat slope” so that edge positionand edge steepness errors take only a slight influence on the overalltransmission. With this provision the effect is achieved that theoverall transmission, which is achieved by a convolution of thetransmission of the path of the illuminating beam with the transmissionof the path of the observation beam and by integration over the relevantwavelength range, will be influenced only slightly by the displacementof the edge position and/or the steepness of the transmission edge.

In accordance with the invention therefore the spectral internaltransmittance or the spectral transmission function T₁(λ), respectively,of the light-feeding unit or the path of the illuminating beam istherefore matched with the fluorescence excitation spectrum of thephoto-amboceptor or of the tissue, respectively, and the spectralinternal transmittance or the spectral transmission function T_(b)(λ),respectively, of the imaging unit or of the path of the observationbeam, respectively, with the fluorescence spectrum of thephoto-amboceptor or the tissue, respectively. Moreover, the transmissionfunction T₁(λ) of the path of the illuminating beam intersects thetransmission function T_(b)(λ) of the path of the observation beam at atransmission value not exceeding 30%.

The invention starts out from the basic idea that the transmittancelevels or the spectral transmission functions, respectively, of thepaths of the illuminating and observation beams intersect in a zonewhere at least one transmittance graph presents a flat slope—at least inthe event of averaging or substitution of the actual graph by a straightline over a wavelength range from 10 to 30 nm—so that a displacement ofone or of both graphs entails only a comparatively slight variation ofthe area enclosed by the two graphs.

To this end it is decisive that there is at least one referencewavelength λ_(r) which is longer by 2Δλ_(s) at maximum or shorter thanthe wavelength λ_(s) at the point of intersection, for which henceapplies

λ_(s)−2Δλ≦λ_(r)≦λ_(s)+2Δλ

and starting out from which the spectral transmission function T₁(λ) ofthe path of the illuminating beam satisfies the following conditions forat least five wavelengths λ_(r), λ_(r)+Δλ, λ_(r)+3Δλ, λ_(r)−Δλ, andλ_(r)−2Δλ:

|T₁(λ_(r) − Δλ) − T₁(λ_(r) − 2Δλ)| >10% |T₁(λ_(r) + Δλ) + T₁(λ_(r) +3Δλ)| <5%, preferably <3% T₁(λ_(r)) >0.5% T₁(λ_(r) − Δλ) >0.5% T₁(λ_(r)− 2Δλ) >0.5% T₁(λ_(r) + Δλ) >0.3% T₁(λ_(r) + 3Δλ) >0.3%

wherein

 4 nm<Δλ<6 nm

and/or the spectral transmission function T_(b)(λ) of the path of theobservation beam satisfies the following conditions for at least fivewavelengths λ_(r), λ_(r)−Δλ, λ_(r)−3Δλ, λ_(r)+Δλ, and λ_(r)+2Δλ:

|T_(b)(λ_(r) + Δλ) − T_(b)(λ_(r) + 2Δλ)| >10% |T_(b)(λ_(r) − Δλ) −T_(b)(λ_(r) − 3Δλ)| <5%, preferably <3% T_(b)(λ_(r)) >0.5% T_(b)(λ_(r)+Δλ) >0.5% T_(b)(λ_(r)+ 2Δλ) >0.5% T_(b)(λ_(r) − Δλ) >0.3% T_(b)(λ_(r) −3Δλ) >0.3%

wherein

4 nm<Δλ<6 nm.

The transmission functions in the light-feeding and the image-producingsection of the inventive apparatus are so selected that only a preciselyset light quantity of the illuminating light, which is reflected on thetissue and has naturally a comparatively high intensity, “arrives”through the imaging apparatus section in the proximal image planewhereas light having a wavelength λ can arrive from the zone wherefluorescence occurs in the proximal image plane only if it comes fromthe illuminated tissue region rather than from the illuminating system.

The inventively selected transmission functions of the path of theilluminating beam and of the path of the observation beam of theapparatus ensure that the illuminated tissue region is so stronglyirradiated with light of a wavelength which is not within the range ofthe fluorescence spectrum, so that the examining person can perceivedetails of the illuminated tissue region independently of thefluorescent radiation on account of the light directly reflected in thiswavelength region, which furnishes a background picture.

In other terms, in accordance with the invention the image of the tissueregion illuminated with exciting light is produced simultaneously bymeans of fluorescent light and reflected illuminating light, with thetwo fractions, which contribute both to the production of the image,being so set in terms of their wavelength and with respect to theirintensity that they will not “interfere” with each other.

It is preferable to have the setting made in such a way that theintensity of the emitted fluorescent light is within the same order asthe overall intensity of the reflected fraction of the exciting light ofthe illuminating system—weighted by the filter characteristic of theobservation system. In a particularly expedient form the setting is madesuch that the two intensities are roughly the same.

It is moreover expedient that the two spectral transmittances intersectat a value less than 10%, preferably at a value less than 5%.

In an improvement of the invention the transmission function of the pathof the illuminating beam has an almost horizontal plateau or a localmaximum within the range λ_(r) . . . λ_(r)+3Δλ and/or the transmissionfunction of the path of the observation beam has an almost horizontalplateau or a local maximum within the range λ_(r) . . . λ_(r)−3Δλ.

When an ALA-induced PPIX has been selected as photo-amboceptor it ispreferable that the spectral transmittance of the path of theilluminating beam satisfies the following relationship

100%>T ₁(λ)400 . . . 420)≦80%

15%>T ₁(λ)440 . . . 455)≦0.5%.

With this configuration of the spectral transmission function of thelight-feeding unit and the imaging unit the effect is achieved that thefluorescent light may be clearly perceived with a high contrast on theimage of the vicinity of a tumour, for instance, which is produced bythe illuminating light.

For an adaptation to the various photo-amboceptors and/or differentdiagnostic conditions or for a conversion of the inventive apparatus toa therapeutic technique it is moreover preferred that the transmissionproperties of the light-transmitting and the imaging units can beadjusted by means of one or several optical elements.

The optical elements which are used to set the transmission functions ofthe light-transmitting and the imaging units are preferably filtersystems such as absorption filters, interference filters or even prismsas well as electrically controllable LC filters (liquid crystal filters)which are adapted for being introduced into the paths of theilluminating and observation beams. In this set-up the expression “pathof the illuminating beam” is understood to denote the optical path fromthe lamp of the light source to the light-feeding unit, through thisunit and from this unit to the tissue region under diagnosis. Theoptical elements and particularly the filter systems may be arranged, onprinciple, at any point of this optical path, preferably at points wherethe optical path is parallel. However, the arrangement between theilluminating system and the light-feeding unit, i.e. ahead of a lightguide fiber bundle, for instance, is particularly preferable. In thedescription of the filter system or systems the internal transmittanceof the respective optical path without filter system is assumed to be100%.

By way of analogy, the expression “path of the observation beam” isunderstood to denote the optical path from the illuminated tissue regionto the imaging unit and from this unit to proximal image plane. (withouta filter system here, too, the internal transmittance is assumed to be100%.) A fine adjustment of the transmission graphs of the paths of theilluminating or observation beam may be effected by means ofsupplementary tilting of the filter elements.

When the inventive apparatus is integrated into an endoscope the imageplane in the endoscope may be located both in the region of the distalend—e.g. when a video chip is used which is disposed on the distalend—and in the region of the proximal end. In the latter case the pathof the observation beam includes, in addition to a lens asimage-receiving optical unit, a relay lens system or a flexible fiberbundle, for instance, as image-transmitting unit. When a relay lenssystem or a fiber bundle is employed as image-transmitting unit thefilter systems introduced into the path of the observation beam arepreferably disposed between the “last flat” of the relay lens system orthe exit facet of the fiber bundle, respectively, and the proximal imageplane.

When the inventive apparatus is integrated into a surgical microscopethe microscope lens system is an element of the imaging unit, which maybe followed, for instance, by a video pickup as electronicimage-recording unit.

The color filters of the video chip are disregarded in the filtercharacteristic. Further filters, which are possibly provided in theoptical path, must, however, also be considered in the determination ofthe internal transmittance.

In another embodiment of the invention the filter, which may beintroduced into the path of the illuminating beam, includes at least twoseparate filters whereof one is a thermoresistant interference filterunit whilst the other one is a thermoresistant heat-absorbing filter.The thermoresistant interference filter unit, in its turn, consistspreferably of a short-pass and a blocking filter, which are disposed onseparate substrates. This leads to distinctly improved transmissionproperties.

In one exemplary embodiment such a filter for use in the path of theilluminating beam of a PDD device, specifically when ALA-induced PPIX isused as photo-amboceptor, presents a spectral transmission functionT₁(λ) which satisfies the following conditions for at least fivewavelengths λ_(r), λ_(r)+Δλ, λ_(r)+3Δλ, λ_(r)−Δλ, and λ_(r)−2Δλ:

|T₁(λ_(r) − Δλ) − T₁(λ_(r) − 2Δλ)| >10% |T₁(λ_(r) + Δλ) + T₁(λ_(r) +3Δλ)| <5%, preferably <3% T₁(λ_(r)) >0.5% T₁(λ_(r) − Δλ) >0.5% T₁(λ_(r)− 2Δλ) >0.5% T₁(λ_(r) + Δλ) >0.3% T₁(λ_(r) + 3Δλ) >0.3%

wherein

4 nm<Δλ<6 nm,

with λ_(r) representing a reference wavelength which is selected as afunction of the respectively used photo-amboceptor or the respectiveautofluorescence, respectively, and for which applies, for instance,when ALA is used as photo-amboceptor:

438 nm−2Δλ≦λ_(r)≦438 nm+2Δλ.

In another exemplary embodiment such a filter for use in the path of theobservation beam in a PDD apparatus, particularly when ALA-induced PPIXis used as photo-amboceptor, has a spectral transmission function T₁(λ)which satisfies the following conditions for at least five wavelengthsλ_(r), λ_(r)−Δλ, λ_(r)−3Δλ, λ_(r)+Δλ, and λ_(r)+2Δλ:

|T_(b)(λ_(r) + Δλ) − T_(b)(λ_(r) + 2Δλ)| >10% |T_(b)(λ_(r) − Δλ) −T_(b)(λ_(r) − 3Δλ)| <5%, preferably <3% T_(b)(λ_(r)) >0.5% T_(b)(λ_(r)+Δλ) >0.5% T_(b)(λ_(r)+ 2Δλ) >0.5% T_(b)(λ_(r) − Δλ) >0.3% T_(b)(λ_(r) −3Δλ) >0.3%

wherein

4 nm<Δλ<6 nm,

with λ_(r) representing a reference wavelength which is selected as afunction of the respectively used photo-amboceptor or the respectiveautofluorescence, respectively, and for which applies, for instance,when ALA-induced PPIX is used as photo-amboceptor:

438 nm−2Δλ≦λ_(r)≦438 nm+2Δλ.

The filter may be an interference filter in particular, having quartz ora heat-resistant glass such as “Schoft Borofloat” as a substratematerial.

When another photo-amboceptor is used the filter properties must beappropriately adapted:

The use of optical elements and filters in particular for taking aninfluence of the transmission characteristic or transmission function,respectively, of the optical path presents the advantage that a normalwhite-light illumination and observation may be performed, for instancewhen the filters are tilted out of the path so that the examiner such asa surgeon can assess the tissue region examined by a fluorescencediagnosis, inter alia by the color. The color is an essential criterionof assessment in the field of ophthalmology, for instance.

Common light sources, and specifically light sources known fromendoscopy, may be used as light sources, too, which emit wide-band lightover the aforementioned wavelength range. Such a light source whichemits light with a sufficient intensity is, for example, a gas dischargelamp and a xenon discharge tube in particular. If in an isolated casethe luminous efficacy of the light source should be insufficient it ispossible to use a “pulsed” light source such as a flash device with aflash lamp or even a laser in addition to a “continuously operating”light source.

BRIEF DESCRIPTION OF THE DRAWING

The invention will be described in the following in more details withreference to the drawing wherein:

FIG. 1 is a schematic view of an inventive apparatus for endoscopicapplications;

FIG. 2 is a schematic representation of the filter characteristic of anembodiment;

FIG. 3 is an enlarged view of the region where the two filter curvesintersect, and

FIG. 4a is an illustration for explaining the advantages of theinvention, and

FIG. 4b is an illustration for explaining the disadvantages of priorart.

DESCRIPTION OF AN EMBODIMENT

FIG. 1 is a schematic view of an embodiment of an inventive apparatusfor endoscopic applications. The reference numeral 1 designates anendoscope which comprises, in a manner known per se, a light-guideconnector 2, a rod-shaped element 3 for introduction into a human body(which is not illustrated here) and an eyepiece 4.

The light guide connector 2 is connected to a light source 6 via a fiberoptic light guide 5, which light source may include, for instance, axenon discharge tube. A light guide 21in the endoscope, which mayconsist of a fiber bundle, for example, passes the light of the lightsource 6, which is fed into the light guide connector 2, to the distalend 11 of the endoscope. The light emerging from the distal end 11illuminates the tissue region 7 to be examined.

The light arriving from the tissue region 7 enters a lens 31 of theendoscope 1, which is illustrated in a schematic form only. The imageproduced by the lens 31 is guided by an image-relaying section 32, whichmay include relay lens systems including rod-shaped lenses or a fibreimaging system, to the proximal end 12 of the endoscope. The image ofthe tissue region 7, which is produced in the proximal image plane 13,may be viewed with the eye through the eyepiece. The image may be shotwith a video camera 8 alternatively or, via a beam splitter, inaddition, for viewing with the eye. FIG. 1 shows the alternative thatthe video camera 8 is attached directly on the eyepiece 4.

As far as described above, the structure is known, for instance, fromthe endoscopes equipped with a video camera, which are manufactured byKarl Storz GmbH & Co., Tuttlingen, Germany. Regarding details of thestructure therefore reference is made to the known endoscopes of thismanufacturer.

Filter systems may be inserted into the path of the illuminating beamand the path of the observation beam so as to perform a so-calledphotodynamic diagnosis.

To this end, a filter system 9 is mounted on the light output terminal61 of the light source 6 in the embodiment illustrated in FIG. 1, withthe fiber optic light guide 5 being flange-mounted on the filter system.The filter system 9 comprises a thermoresistant interference filter 91and a thermoresistant heat-absorbing filter 92 which is intended toreduce the thermal load on the interference filter 91 substantially. Afilter 93 is mounted ahead of the video camera 8, too.

The exposure setting of the video camera 8 and the light emission fromthe light source 6 are controlled by a control and evaluating unit 10.The control and evaluating unit 10 may, for instance, be suitable tosynchronise a photoflash source with the light integration phase of aCCD chip in the video camera 8. Moreover, the control and evaluatingunit 10 may control the luminous power emitted from the light source 6and/or the exposure setting of the video camera.

Furthermore, the output signal of the video camera 8 is applied to thecontrol and evaluating unit 10. The evaluating unit may comprise, inparticular, an image processing system which processes the video cameraoutput signal in the manner described by way of introduction and whichdisplays the image-processed output signal on a monitor. The outputsignal directly output by the video camera and/or image-processed may,of course, also be stored in a device such as a recorder and/or in animage data base or processed further in any other way by means ofelectronic data processing systems.

When a photo-amboceptor is used the tissue region 7 emits both reflectedilluminating light and fluorescent light which is created by thelight-induced reaction in biologic systems, which is created by thephoto-amboceptor. In order to be able to detect the fraction offluorescent light, which is small compared to the reflected fraction,and to distinguish it reliably from the “non-fluorescent light” in thesubsequent image processing step an appropriately selected transmissioncharacteristic of the paths of the illuminating and the observationbeams is required. For setting the transmission characteristic duringthe photodynamic diagnosis the filters 91 and 93 are provided which maybe introduced into the optical path. As the filters may be removedagain, e.g. by tilting them out of the optical paths, a normalobservation of the tissue region 7 is possible, too, without any risk ofeffects, such as color distortion.

With reference to FIG. 2 how the characteristic of the filters 91 and 93will be explained in the following. In these figures the characteristicsof the filters in the path of the illuminating beam (excitation filter)and in the observation beam (observation filter) are described for oneembodiment with reference to the case that δ-aminolaevuic acid is usedas photo-amboceptor. When other photo-amboceptors are used the filtercharacteristic must be adapted correspondingly.

Regarding the numerical values of the transmission values or thespectral transmittance T(λ) (in %) as a function of the wavelength λreference is made explicitly to these Figures.

It is apparent from FIG. 2 that the transmission of the excitationfilter presents a steep drop towards longer wavelengths fromapproximately 425 nm onwards. By contrast to the filter characteristicdescribed in the PCT application PCT/DE96/01831, the transmission atwavelengths longer than roughly 450 nm is practically not zero butexceeds rather 0.5 & over a range of at least 10 nm, however it issmaller than 5% (cf. FIG. 3).

This flat run-out over a major wavelength range of the transmissiongraph of the excitation filter substantially determines the overlappingof the two transmission graphs, i.e. the quantity of the transmittedlight which the observer perceives as “background picture” in additionto the induced fluorescent light.

A displacement of one of the two graphs as a result of manufacturingfaults etc. hence takes a substantially smaller influence on thetransmitted quantity of light than is the case in prior art.

This is illustrated by FIG. 4a where, in addition to the desirablecharacteristic of the observation filter, an “actual characteristic” isindicated in dashed lines which is due to manufacturing faults and inwhich the filter graph is shifted by a defined wave length λ. As isapparent from FIG. 4b the fault takes only a slight influence on thetransmitted quantity of light.

For comparison, FIG. 4b shows the variation occurring in prior art wherethe transmission of the excitation filter does not present an inventiveplateau but drops to zero directly. With the shift of the transmissionsby the of light which contributes to the background picture is reducedsubstantially more strongly than in the invention.

What is claimed is:
 1. A system for diagnosis or therapeutic treatmentby means of a light-induced reaction created in biologic tissue “invivo”, comprising a path of an illuminating beam constituted by at leastone light source with a lamp system generating incoherent light in awavelength range of at least 400 to 650 nm, and a light-feeding unitwhich directs the light of the at least one light source onto a tissueregion to be diagnosed or therapeutically treated, presenting a spectraltransmission function T₁(λ) matched with the fluorescence excitationspectrum of the light-induced reaction and a path of an observation beamconstituted by an imaging unit which images the light coming from saidtissue region into an image plane, presenting a spectral transmissionfunction T_(b)(λ) matched with the fluorescence spectrum of thelight-induced reaction wherein said spectral transmission function T₁(λ)of said path of the illuminating beam and said spectral transmissionfunction T_(b)(λ) of said path of the observation beam intersect atwavelength λ_(s) at which the transmission value of each optical path isnot higher than 30%, wherein at least one reference wavelength λ_(r) isprovided which is longer by up to 2Δλ at maximum or smaller than thewavelength λ_(s) at the point of intersection, for which hence applies:λ_(s)−2Δλ≦λ_(r)≦λ_(s)+2Δλ  and starting out from which the spectraltransmission function T₁(λ) of the path of the illuminating beamsatisfies the following conditions for at least five wavelengths λ_(r),λ_(r)+Δλ, λ_(r)+3Δλ, λ_(r)−Δλ, and λ_(r)−2Δλ: |T₁(λ_(r) − Δλ) − T₁(λ_(r)− 2Δλ)| >  10% |T₁(λ_(r) + Δλ) + T₁(λ_(r) + 3Δλ)| <   5% T₁(λ_(r)) >0.5% T₁(λ_(r) − Δλ) > 0.5% T₁(λ_(r) − 2Δλ) > 0.5% T₁(λ_(r) + Δλ) > 0.5%T₁(λ_(r) + 3Δλ) > 0.3%

 wherein 4 nm<Δλ<6 nm.
 2. System according to claim 1, wherein saidreference wavelength λ_(r) equals the wavelength λ_(s) at the point ofintersection.
 3. System according to claim 1, wherein said twotransmission functions T₁(λ) and T_(b)(λ) intersect at a transmissionvalue less than 10%.
 4. System according claim 1, wherein said spectraltransmission function T₁(λ) of said path of the illuminating beampresents an almost horizontal plateau within the range λ_(r) . . .λ_(r)+3Δλ.
 5. System according to claim 1, wherein said spectraltransmission function T₁(λ) of said path of the illuminating beampresents a local maximum within the range λ_(r) . . . λ_(r)+3Δλ. 6.System according to claim 1, wherein the spectral transmission functionof said light feeding unit and said imaging unit are variable by meansof one or several optical elements.
 7. System according to claim 6,wherein said optical elements are interference filters.
 8. Systemaccording to claim 1, wherein the spectral transmission functions are soset that the overall intensity of induced fluorescent light is withinthe same order as the overall intensity of a light fraction of theilluminating system, which is reflected directly on the tissue region.9. System according to claim 1 wherein said imaging unit comprises animager and an image recording unit.
 10. System according to claim 1wherein said imaging unit comprises an imager and an image-transmittingunit.
 11. System according to claim 1, wherein said two transmissionfunctions T₁(λ) and T_(b)(λ) intersect at a transmission value less than5%.
 12. System according to claim 1, wherein the light-induced reactionis created by a photo-amboceptor.
 13. System according to claim 12,wherein when ALA is used as a photo-amboceptor said spectraltransmission function T₁(λ) of said path of the illuminating beamsatisfies the following relationship: 100%>T ₁(λ) 400 . . . 420)≧80%15%>T ₁(λ) 440 . . . 455)≧0.5%.
 14. System according to claim 1, whereinthe light-induced reaction is created by autofluorescence.
 15. A systemfor diagnosis or therapeutic treatment by means of a light-inducedreaction in biologic tissue “in vivo”, comprising a path of anilluminating beam constituted by at least one light source with a lampsystem generating incoherent light in a wavelength range of at least 400to 650 nm, and a light-feeding unit which directs the light of the atleast one light source onto a tissue region to be diagnosed ortherapeutically treated, presenting a spectral transmission functionT₁(λ) matched with the fluorescence excitation spectrum of thelight-induced reaction, and a path of an observation beam constituted byan imaging unit which images the light coming from said tissue regioninto an image plane, presenting a spectral transmission functionT_(b)(λ) matched with the fluorescence spectrum of the light-inducedreaction wherein said spectral transmission function T₁(λ) of said pathof the illuminating beam and said spectral transmission functionT_(b)(λ) of said path of the observation beam intersect at wavelengthλ_(s) at which the transmission value of each optical path is not higherthan 30%, wherein at least one reference wavelength λ_(r) is providedwhich is longer by up to 2Δλ at maximum or smaller than the wavelengthλ_(s) at the point of intersection, for which hence applies:λ_(s)−2Δλ≦λ_(r)≦λ_(s)+2Δλ  and starting out from which the spectraltransmission function T_(b)(λ) of the path of the observation beamsatisfies the following conditions for at least five wavelengths λ_(r),λ_(r)−Δλ, λ_(r)−3Δλ, λ_(r)+Δλ, and λ_(r)+2Δλ: |T_(b)(λ_(r) + Δλ) −T_(b)(λ_(r) + 2Δλ)| >  10% |T_(b)(λ_(r) − Δλ) − T_(b)(λ_(r) − 3Δλ)| <  5% T_(b)(λ_(r)) > 0.5% T_(b)(λ_(r) + Δλ) > 0.5% T_(b)(λ_(r) + 2Δλ) >0.5% T_(b)(λ_(r) − Δλ) > 0.3% T_(b)(λ_(r) − 3Δλ) > 0.3%

 wherein 4 nm<Δλ<6 nm.
 16. System according to claim 15, wherein saidreference wavelength λ_(r) equals the wavelength λ_(s) at the point ofintersection.
 17. System according to claim 15, wherein said twotransmission functions T₁(λ) and T_(b)(λ) intersect at a transmissionvalue less than 10%.
 18. System according claim 15, wherein saidspectral transmission function T_(b)(λ) of said path of the observationbeam has an almost horizontal plateau within the range λ_(r) . . .λ_(r)−3Δλ.
 19. System according to claim 15, wherein said spectraltransmission function T_(b)(λ) of said path of the observation beampresents a local maximum within the range λ_(r) . . . λ_(r)−3Δλ. 20.System according to claim 15, wherein the spectral transmission functionof said light feeding unit and said imaging unit are variable by meansof one or several optical elements.
 21. System according to claim 20,wherein said optical elements are interference filters.
 22. Systemaccording to claim 15, wherein the spectral transmission functions areso set that the overall intensity of induced fluorescent light is withinthe same order as the overall intensity of a light fraction of theilluminating system, which is reflected directly on the tissue region.23. System according to claim 15 wherein said imaging unit comprises animager and an image recording unit.
 24. System according to claim 15wherein said imaging unit comprises an imager and an image-transmittingunit.
 25. System according to claim 15, wherein said two transmissionfunctions T₁(λ) and T_(b)(λ) intersect at a transmission value less than5%.
 26. System according to claim 15, wherein the light-induced reactionis created by a photo-amboceptor.
 27. System according to claim 26,wherein when ALA is used as a photo-amboceptor said spectraltransmission function T₁(λ) of said path of the illuminating beamsatisfies the following relationship: 100%>T ₁(λ) 400 . . . 420)≧80%15%>T ₁(λ) 440 . . . 455)≧0.5%.
 28. System according to claim 15,wherein the light-induced reaction is created by autofluorescence.